The Eighth Annual International Meeting for Autism Research (IMFAR), held this year in Chicago, Ill., kicked off on Thursday with scientists from around the world gathering to share their latest research information. The goal of those in attendance is to use research methodology to develop means of helping individuals living with autism and their families have a better quality of care and life.
Below are just a few select studies from last Saturday's presentations. A full report of the conference will be issued in Autism Speaks e-speaks newsletter this week. Click here to register for e-speaks.
Highlights from Day Three: Saturday, May 9, 2009
In searching for genetic contributions to autism, keynote speaker Stephen Scherer, Ph.D. (The Hospital for Sick Children), described a new type of genetic variability called CNVs, or copy number variations. CNVs involve the loss or gain of segments of DNA, which effectively changes the number of gene copies a person has. Normally we have two – one from each parent – but a CNV in the genome results in the wrong number of gene copies. Having either too many or too few gene copies disrupts the levels of proteins made from these genes, which can have big repercussions in the brain. CNVs are rare "big hits" to the genome relative to the smaller changes in single base pairs in genes (SNPs), which have been the subject of intensive focus in autism.
Dr. Scherer showed how evidence is mounting for CNV involvement in autism as well. CNVs are found in people with autism more frequently than those without the disorder. However, drawing a definitive connection between particular CNVs and autism is hampered by their surprising prevalence in the general population, and variable phenotypes of those with similar CNVs. Overlooked until very recently, CNVs can now be considered an important risk factor for autism.
Spurred by a growing interest in a role for the immune system in autism, a special educational symposium today highlighted how immune system molecules called antibodies can interact with the nervous system, and produce clear changes in behavior. Normally, antibodies help us fight off infection, but in some cases, antibodies can turn against us, targeting our own tissues instead of pathogens; these renegade "autoantibodies" cause autoimmune diseases like lupus or multiple sclerosis. Several scientists at the meeting are exploring whether autoantibodies that target the brain early in development may lead to autism.
Robert Fujinami, Ph.D. (Univ. of Utah School of Medicine), educated the audience on how the immune system can mount immune responses against the nervous system. Bruce Volpe, M.D., (Weill Medical College of Cornell Univ.), described how patients with lupus have an autoantibody that targets the NMDA receptor, which is involved in transmitting electrical signals between neurons. This antibody could disrupt the receptor's function, which is known to be essential for normal learning and memory. Dr. Volpe also finds that the level of these autoantibodies correlates with impaired brain function.
The normally beneficial role of the immune system extends into pregnancy, where a mother's antibodies pass to her developing fetus. Scientists have been finding that a small subset of mothers who have children with autism also have antibodies that target fetal brain tissue, which they hypothesize may disturb fetal brain development in utero. David Amaral, Ph.D., (UC Davis), has tested the effect of these maternal antibodies in rhesus monkeys in utero, and finds that the offspring exposed to the autoantibodies go on to develop hyperactive and stereotyped movements one year after birth.
Environmental Factors in Autism
Because genetic factors, exposures to environmental toxins, and interactions between both could contribute to autism, scientists are searching for environmental factors that increase risk for autism. Several studies today considered the role of mercury in autism. Concepción Martín-Arribas, (Carlos III Health Institute, Spain), presented the results of the first ever case-control study on environmental risk factors and autism in Spain. Questionnaires about environmental exposures did not reveal any differences between the autism and control groups, nor did hair tests of mercury levels. Low birth weight, however, was associated with an increased risk for autism, highlighting the possibility that prenatal factors may come into play.
A presentation by Jennifer Nyland, Ph.D. (Univ. of S.C. School of Medicine), explored whether mercury can induce abnormal immune responses in pregnant mothers and their fetuses. By studying a unique population in Brazil that has high mercury exposures due to fish consumption in a region rife with mining, she found increased antibody production in the blood of pregnant mothers or in blood derived from the umbilical cord of their babies. Antibody levels were associated with mercury levels, which suggests that pregnant mothers and their babies are more sensitive to mercury than the rest of the population
Finally, epidemiologist Irva Hertz-Picciotto, Ph.D. (UC Davis), re-examined previous studies that did not find a link between autism and thimerosal, a mercury-based preservative found in some childhood vaccines until recently. Three studies had minor design flaws that might have underestimated the number of cases of autism. Although these critiques may not have necessarily influenced the final outcome of the studies, Dr. Hertz-Picciotto explained that they highlight the importance of extremely careful study design in epidemiology.
Gender Differences in Autism
Males with autism outnumber females, and this imbalance may hold important clues into the biological basis of the disorder. To address this, several studies compared the symptoms of autism between males and females. David Mandell, Sc.D. (UPenn School of Medicine), and his group did not find any differences in verbal scores, nonverbal scores, or spatial abilities between school age boys and girls with autism. Another by Harry Wright, M.D. (Univ. of S.C. School of Medicine) , did not find a difference in problem behaviors displayed by boys and girls with autism. Finally, a study by Deborah Fein, Ph.D. (U. Conn.), and colleagues tracked gender differences in cognitive functioning over time (between two and four years of age) and failed to find any differences in trajectories. They believe their data may ultimately point to a consistent underdiagnosis of autism in young girls, especially high-functioning ones.
On the other hand, an interesting study by A. V. Hall (Univ. of S.C. School of Public Health), showed that males and females receive a diagnosis of autism through different sets of symptoms. For example, females exhibit more deficits in socio-emotional reciprocity, but fewer preoccupations with objects than males. Refining the picture of gender differences in autism in future studies will be important for understanding the biological basis of autism, for diagnosing it appropriately, and for customizing treatments. Moreover, due to the gender bias, girls with autism have traditionally not been as well studied as males, and it will be important to understand if they have any special needs not being addressed..
Imaging Connections in Autism
Autism is emerging as a disorder of connectivity, meaning that connections between neurons are not functioning as they typically do. Such connections normally allow disparate parts of the brain to talk to each other and to integrate incoming information appropriately. If connections are miswired, then this can misdirect or impede the signals flowing in the brain, with big effects on behavior. Different kinds of evidence suggest that the brain in autism has a number of connectivity abnormalities, and new brain scanning techniques now allow scientists to examine connections between neurons in people with autism.
The axons that connect one neuron to another often follow the same paths in the brain to reach their targets, running together in bundles often referred to as tracts of white matter. Using a technique called diffusion tensor imaging, scientists are finding that the tracts that connect distant parts of the brain are consistently smaller in people with autism when compared to those without the disorder, suggesting a decrease in the number of connections. Andrew Alexander, Ph.D. (Univ. of Wisc.), found evidence for impaired long range connections in a study of high functioning individuals with autism. Emphasizing the point that these structural changes in the brain can shape behavior, he found a correlation between white matter structure and scores on the social responsiveness scale, a standard measure of social abilities. The more reduced the tract, the more impaired in social abilities. Similarly, Anne Bargiacchi, Ph.D. (CEA-INSERM, France) found a correlation between aberrations in the main pathways of the social brain network and symptom severity of autism. These abnormalities likely reflect disruptions during development when the brain is becoming wired together, and getting a clearer picture of the structure of these tracts can improve our understanding of brain function in autism and how it may be modulated.
View a recap of day one, Thursday, May 7 here.
View a recap of day two, Friday, May 8 here.
Read a press release about the conference here.
View press coverage of the conference here.
To read individual abstracts, please visit: http://imfar.confex.com/imfar/2009/webprogram/start.html